PMID- 35874544
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221231
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 13
DP  - 2022
TI  - Impairment of Ceramide-Mediated Endothelial Instant Membrane Resealing During 
      Diabetes Mellitus.
PG  - 910339
LID - 10.3389/fphys.2022.910339 [doi]
LID - 910339
AB  - Recent studies have indicated that instant cell membrane resealing (ICMR) 
      controls the activation of NOD-like receptor pyrin domain containing 3 (Nlrp3) 
      inflammasomes in endothelial cells, thereby initiating and promoting vascular 
      inflammation. It remains unknown whether this impaired ICMR occurs under diabetic 
      condition or hyperglycemia contributing to endothelial dysfunction leading to 
      vascular inflammation, a hallmark of diabetic vascular injury. The present study 
      aims to examine whether ICMR occurs during in control and diabetic mice and to 
      explore related molecular mechanisms associated with acid sphingomyelinase 
      (ASM)-mediated ceramide production. Using confocal microscopy, we demonstrated 
      that mouse aortic endothelial cells (MAECs) exposed to high glucose levels 
      exhibited much more retarded ICMR after laser-induced membrane injury, compared 
      to that in control cells. The high glucose-induced impairment of membrane 
      resealing in MAECs was prevented when these cells were pretreated with 
      sphingomyelin or C24-ceramide. Mechanistically, high glucose treatment decreased 
      association of membrane ceramide with annexin A5, an essential element of 
      membrane repair machinery. Consistently, the association of ceramide with annexin 
      A5 was significantly reduced in the coronary arterial endothelium of mice with 
      streptozotocin-induced diabetes mellitus compared to that in non-diabetic control 
      mice. Moreover, a marked reduction of the association of ceramide with annexin A5 
      was observed in coronary arterial endothelium of ASM knockout mice regardless of 
      their diabetic status. Lastly, high glucose treatment or ASM gene deletion 
      substantially impaired ICMR in coronary arterial endothelium of mice receiving 
      membrane puncturing agents. Collectively, our data suggest that ceramide-mediated 
      ICMR in vascular endothelial cells is impaired during diabetes mellitus due to 
      dissociation of ceramide with annexin A5 and ASM play a critical role in this 
      ICMR.
CI  - Copyright (c) 2022 Chen, Li, Bhat, Li, Zhang and Li.
FAU - Chen, Yang
AU  - Chen Y
AD  - School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, 
      Guangzhou, China.
AD  - Department of Pharmacology and Toxicology, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, United States.
FAU - Li, Guangbi
AU  - Li G
AD  - Department of Pharmacology and Toxicology, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, United States.
FAU - Bhat, Owais M
AU  - Bhat OM
AD  - Department of Pharmacology and Toxicology, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, United States.
FAU - Li, Xiang
AU  - Li X
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, TX, United States.
FAU - Zhang, Yang
AU  - Zhang Y
AD  - Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, 
      University of Houston, Houston, TX, United States.
FAU - Li, Pin-Lan
AU  - Li PL
AD  - Department of Pharmacology and Toxicology, School of Medicine, Virginia 
      Commonwealth University, Richmond, VA, United States.
LA  - eng
GR  - R01 HL057244/HL/NHLBI NIH HHS/United States
GR  - R01 HL075316/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20220706
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC9298829
OTO - NOTNLM
OT  - annexin
OT  - endothelial dysfunction
OT  - hyperglycemia
OT  - membrane repair
OT  - sphingolipid
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/07/26 06:00
MHDA- 2022/07/26 06:01
PMCR- 2022/07/06
CRDT- 2022/07/25 03:54
PHST- 2022/04/04 00:00 [received]
PHST- 2022/06/14 00:00 [accepted]
PHST- 2022/07/25 03:54 [entrez]
PHST- 2022/07/26 06:00 [pubmed]
PHST- 2022/07/26 06:01 [medline]
PHST- 2022/07/06 00:00 [pmc-release]
AID - 910339 [pii]
AID - 10.3389/fphys.2022.910339 [doi]
PST - epublish
SO  - Front Physiol. 2022 Jul 6;13:910339. doi: 10.3389/fphys.2022.910339. eCollection 
      2022.